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Historically, tumor biopsies and clinical laboratory testing have been the gold standard for diagnosis and prognosis in metastatic renal cell carcinoma (mRCC). Genomic profiling in mRCC has traditionally been performed on tumor tissue; however, challenges and limitations in obtaining tissue biopsies led to the discovery of alternative biological specimens, namely circulating cell-free DNA (cfDNA). Rapidly evolving technologies, with increased sensitivity and specificity, have been used to query cfDNA in the clinical research setting. These investigations are rapidly establishing cfDNA and liquid biopsies as valuable complementary specimens to the gold standard, and in some instances surpassing these with unique insight into the contemporary genomic landscape and tumor heterogeneity. In this review, we will discuss recent research into the prognostic, diagnostic, and predictive utility of liquid biopsies in mRCC. We will explore their potential role in precision treatment of mRCC and conclude with what is needed in order to translate them to clinical practice.

Cell-free Circulating Tumor DNA (ctDNA) in Metastatic Renal Cell Carcinoma (mRCC): Current Knowledge and Potential Uses